Testosterone injection, but not oral testosterone, effective in men with low testosterone and metabolic syndrome or diabetes

This study compared the effects of the long-acting testosterone undecanoate injection with those of oral testosterone undecanoate capsules in 52 men (mean age 57 years) with hypogonadism (low testosterone) and symptoms of the metabolic syndrome (MetS) and/or type 2 diabetes mellitus. For the first 6 months of the study, two similar groups of men received either the testosterone injection every 12 weeks or testosterone undecanoate capsules twice daily. There was a third, control, group of men who received a dummy drug (placebo). After 6 months, the oral testosterone group was switched over to receive 6 months of treatment with the testosterone injection, while the other groups continued with their original treatment for another 6 months.

Key Findings

During the first 6 months, treatment with the testosterone injection:

Returned testosterone levels to normal values (see Figure)

Improved the body’s sensitivity to insulin

Had a beneficial effect on waist circumference and body fat

Improved sexual function

There were additional improvements in these results when treatment with the testosterone injection was continued for another 6 months

In contrast, 6 months of treatment with testosterone capsules did not improve any of the factors investigated in the study

However, after switching from oral testosterone to the testosterone injection for the second 6 months of the study, testosterone levels (see Figure), insulin sensitivity, waist circumference and levels of body fat all improved

In the placebo group, there were no differences in these measures between the start (baseline) end of the study.

Background information

This study is important as it shows that not all formulations of testosterone are equally effective. The study showed for the first time that oral testosterone capsules were ineffective in these men with low testosterone and MetS and/or diabetes. Unlike testosterone capsules, which have to be taken twice a day, the long-acting testosterone injection brings testosterone levels back into the normal range and keeps them there with only four or five administrations per year. As well as being more convenient, the study showed that the injection also was much more effective in improving testosterone deficiency symptoms.

This is important, as studies have shown that having low testosterone levels can increase the risk of cardiovascular disease, diabetes, the MetS and narrowing of the arteries (atherosclerosis), and that there is a link between low testosterone and diabetes and the MetS. Returning testosterone levels to normal in men with low testosterone and MetS and/or diabetes can help to improve a number of features of MetS and have a beneficial effect on fat levels and body composition. This suggests that testosterone replacement therapy may have a role in preventing and/or treating MetS and reducing the risk of cardiovascular disease and other associated diseases, such as diabetes and narrowing of the arteries.

Metabolic syndrome (MetS) is a group of risk factors for cardiovascular diseases and diabetes linked to being overweight or obese: three or more of these conditions together is sufficient for a diagnosis of metabolic syndrome. These conditions or characteristics are:

A large waistline (which is linked to insulin resistance)

A higher than normal fat level in the blood – in particular raised levels of triglycerides

A lower than normal level of ‘good’ high-density lipoprotein (HDL) cholesterol in the blood

Higher than normal blood pressure

Higher than normal blood sugar levels.

Visceral fat is the hard-to-lose fat around the internal organs that makes people more susceptible to heart disease, stroke, diabetes and high blood pressure.